Combination Therapy Manuscript
Data
df <- readRDS("./data/dataset/df.RDS")
# Canonical
canonical <- readRDS("./data/carbapenem_resistance_panel/carbapenem_resistance_panel_matrix.RDS")
df <- left_join(df,canonical)
# tn4401 data
tn4401 <- readRDS("./data/TETyper/TETyper_curated.RDS")
df <- left_join(df,tn4401)
# load the kleborate
kleborate <- readRDS("./data/kleborate/kleborate_curated.RDS") %>% as.data.frame
df <- left_join(df,kleborate)
tr <- read.tree("./data/tree/tree.treefile")
nn <- readRDS("./data/nearest_neighbor_comparisons/nn_comparisons.RDS")
blbli_asr <- readRDS("./data/asr_clustering/blbli_asr_clustering_df.RDS")
df <- df %>% left_join(.,blbli_asr)
df$blbli_clustering_simple <- recode(df$blbli_asr_cluster_renamed,"No Feature"="Susceptible")
drug_entry <- c('OmpK35-25%','OmpK36_c25t','OmpK36GD','OmpK36TD','OmpK36_truncation_kleborate','OmpK36_non_syn','OmpK36_putative_function_altering','OmpK36_intergenic','OmpK36_promoter_IS')
drug_exit <- c("AcrAB_TolC_any",'RamR',"RamA")
target_modification <- c('PBP_any','PBP2',"PBP4")
carbapenem <- c(drug_entry,drug_exit,target_modification)
FA - phylogeny
FB - non freq s
variables_to_use <- carbapenem %>% subset(.!='OmpK35-25%')
gwas_nons_freq <- variants_freq(variables_to_use,df)
gwas_nons_freq$locus_tag<- factor(gwas_nons_freq$locus_tag, levels=rev(unique(variables_to_use)))
gwas_nons_freq$`Significant Hit` <- recode(gwas_nons_freq$locus_tag ,'OmpK35-25'='ompK35 porin truncation at 25%','OmpK36_c25t'='C25T mutation in ompK36','OmpK36_L3_mutations'='Loop 3 insertion in ompK36','OmpK36GD'='GD insertion in loop 3 of ompK36','OmpK36TD'='TD insertion insertion in loop 3 of ompK36','OmpK36_truncation_kleborate'='ompK36 truncation', 'OmpK36_non_syn'='ompK36 non-synonymous mutation','OmpK36_putative_function_altering'='ompK36 putative function-altering mutations (PFAV)','OmpK36_intergenic'='Variant in intergenic region of ompK36','OmpK36_promoter_IS'='Insertion seqeunce at ompK36 promoter',"AcrAB_TolC_any" = 'acrAB-tolC efflux pump mutant','RamR'='ramR efflux pump regulator PFAV',"RamA"='ramA efflux pump activator PFAV','PBP_any'='Non-synonymous mutations in penicillin-binding-proteins','PBP2'='Penicillin-binding protein-2',"PBP4"='Penicillin-binding protein-4')
figure_3.C <- freq_plot(gwas_nons_freq)
FB <- freq_plot(gwas_nons_freq)
FC - nn data
# C. FC MIC (MVB * IR overlay)
nn_data_melt <- lapply(variables_to_use,generate_nn_melt_data,nn_data=nn) %>% do.call(rbind,.)
nn_data_melt$locus_tag <- factor(nn_data_melt$locus_tag, levels=rev(unique(variables_to_use)))
nn_data_melt$locus_tag<- factor(nn_data_melt$locus_tag, levels=rev(unique(variables_to_use)))
nn_data_melt$locus_tag<- recode(nn_data_melt$locus_tag ,'OmpK35-25'='ompK35 porin truncation at 25%','OmpK36_c25t'='C25T mutation in ompK36','OmpK36_L3_mutations'='Loop 3 insertion in ompK36','OmpK36GD'='GD insertion in loop 3 of ompK36','OmpK36TD'='TD insertion insertion in loop 3 of ompK36','OmpK36_truncation_kleborate'='ompK36 truncation', 'OmpK36_non_syn'='ompK36 non-synonymous mutation','OmpK36_putative_function_altering'='ompK36 putative function-altering mutations (PFAV)','OmpK36_intergenic'='Variant in intergenic region of ompK36','OmpK36_promoter_IS'='Insertion seqeunce at ompK36 promoter',"AcrAB_TolC_any" = 'acrAB-tolC efflux pump mutant','RamR'='ramR efflux pump regulator PFAV',"RamA"='ramA efflux pump activator PFAV','PBP_any'='Non-synonymous mutations in penicillin-binding-proteins','PBP2'='Penicillin-binding protein-2',"PBP4"='Penicillin-binding protein-4')
FC <- nn_plot(nn_data_melt)
FBC <- plot_grid(FB,FC ,nrow = 2,labels = c("B.","C."),label_size = 62,align = "hv",label_x = -0.02) + theme(plot.margin = unit(c(t=0,r=0,b=0,l=0.1), "cm"))
FABC <- plot_grid(FA,FBC,labels = c("A.",""),label_size = 62,ncol = 2,rel_heights = c(1,0.75),rel_widths = c(1,0.4)) + theme(plot.margin = unit(c(0,0,0,0), "cm"))
FABC
